The objectives of this proposal are: (1) to define the role of various host immune factors in primary and recurrent infections with oral herpes simplex virus type 1 (HSV-1); (2) to evaluate the effectiveness of BCG and of transfer factor in reducing herpetic recurrences, and; (3) to attempt to correlate any benefit from these regimens with specific immune responses. Longitudinal immunological, virological and clinical studies will be conducted on individuals: (1) with primary HSV-1 infections; (2) with infrequent HSV recurrences; (3) with very frequent HSV recurrences and in (4) immunocompromised hosts with primary or recurrent HSV infections. Immunological assays include tests for neutralization, passive hemagglutination and IgM, IgA and IgG antibodies to HSV and assays for cell mediated immunity, including lymphocyte transformation, lymphocytotoxin, interferon and leukocyte migration inhibition tests. Assays for detecting the number of lymphocytes sensitized to HSV-1 and for demonstrating direct cytotoxicity of lymphocytes to cells with surface HSV antigens will be developed. In addition, isolation of HSV from peripheral leukocytes will be attempted, and the interactions of HSV with macrophages in vitro and the effect of BCG on HSV infection in mice will be studied. These investigations should provide basic information necessary to the possible use of immunoprophylaxis or immunotherapy of a viral infection which afflicts a large number of people and which has been associated with human cancer.